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Issue 8, 2011
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PNA-based artificial nucleases as antisense and anti-miRNA oligonucleotide agents

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Abstract

Because of its interesting chemical, physical and biological properties, Peptide Nucleic Acid (PNA) has attracted major attention in molecular biology, for diagnostics purposes and development of biosensors. PNAs have become candidates for gene therapeutic drugs in ANTISENSE (AO) strategy with favorable in vivo biochemical properties. Recently, antisense PNA oligonucleotides have been described in anti-miRNA approach (AMO). We propose PNA-based nucleases as AO and AMO agents. We report the design, synthesis and characterization of two kinds of artificial nucleases composed of a PEG–PNA–PEG domain conjugated to HGG·Cu (A) and DETA (B) as well known cleavage sites. Qualitative (MALDI-TOF) and quantitative (HTS) assays were planned to study nuclease activity of constructs A and B on RNA–3′-FAM target sequence. The results have highlighted the best performance of nuclease B and the relevance of the PEG spacer, in particular for conjugate A, in terms of efficiency of the cleavage, suggesting that conjugates A and B also act as potential antisense and anti-miRNA agents.

Graphical abstract: PNA-based artificial nucleases as antisense and anti-miRNA oligonucleotide agents

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Publication details

The article was received on 03 Apr 2011, accepted on 04 May 2011 and first published on 27 May 2011


Article type: Paper
DOI: 10.1039/C1MB05131H
Citation: Mol. BioSyst., 2011,7, 2490-2499
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    PNA-based artificial nucleases as antisense and anti-miRNA oligonucleotide agents

    M. Gaglione, G. Milano, A. Chambery, L. Moggio, A. Romanelli and A. Messere, Mol. BioSyst., 2011, 7, 2490
    DOI: 10.1039/C1MB05131H

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